What are the best management strategies for radiation-induced xerostomia?

Abstract

What are the best management strategies for radiation-induced xerostomia? The most common long-term complication of radiation therapy (RT) for head and neck cancer is dry mouth or xerostomia.1 Salivary glands are radiosensitive; their destruction begins shortly after the initiation of therapy with the extent of injury directly related to the amount of radiation to which they are exposed.1 The subsequent xerostomia is challenging to manage, leads to multiple and often long-term oral complications, and can significantly impair patients' quality of life. This article utilizes comprehensive review of literature, identified through publicly available search engines, to outline the current best practice recommendations for patients with RT-induced xerostomia. Ideally, attempts are made to prevent xerostomia related to head and neck RT by the use of intensity modified radiation therapy (IMRT), amifostine and/or salivary gland transplantation. Despite such prevention strategies, a significant number of patients develop varying degrees of xerostomia.1, 2 The current therapies for management of RT-induced xerostomia include: 1) stringent oral hygiene with fluoride agents and antimicrobials to prevent dental caries and infections, 2) salivary substitutes, and 3) sialagogues to stimulate saliva production from remaining viable salivary gland parenchyma. In addition, acupuncture is showing therapeutic promise. Salivary substitutes include sprays, gels, and mouthwashes of varying formulations (e.g., mucin and hydroxyethyl cellulose). A review in 2009 by Hanel et al. suggests that mucin-based salivary substitutes may be particularly beneficial for RT-induced xerostomia. Furthermore, this study indicates that in moderate to severe xerostomia, a gel-like saliva substitute may be beneficial at night, while a less viscous formula can be used during the day.3 The oldest, most studied, and only FDA-approved direct cholinergic stimulant for RT-induced xerostomia is pilocarpine. Pilocarpine decreased xerostomia symptoms and increased salivary flow rates in post-RT patients when administered for 8 to 12 weeks with doses >2.5 mg, 3 times daily.2 Similarly, in a randomized controlled trial of 255 post-RT patients, Chambers et al. evaluated the parasympathetic agonist, Cevimeline, which is approved for the treatment of xerostomia in Sjogren's syndrome. This study showed improvement in up to 50% of patients when Cevimeline was administered for 52 weeks.4 Unfortunately, many patients are either not candidates for cholinergic stimulation, due to concurrent medical conditions, or are unable to tolerate the side effects, which include sweating, nausea, and diarrhea. The role of acupuncture in the treatment of RT-induced xerostomia is expanding. Blom et al. compared small groups of patients with sham versus true acupuncture, with both groups showing improvement of salivary flow.5 In 2012, Meng et al. published the first randomized controlled trial comparing standard oral care to acupuncture in patients with nasopharyngeal carcinoma treated with radiation therapy. Acupuncture was administered 3 times weekly for 7 weeks throughout the course of RT. Outcomes were measured by sialometry and a subjective questionnaire. In this study, a statistically significant benefit was observed with increased salivary flow, and subjective improvement in symptom scores at 6 and 11 weeks.5 Of importance, this trial only included patients with nasopharyngeal carcinoma, which is often treated via different radiation portals than other head and neck mucosal primaries. Therefore, care must be taken when attempting to extrapolate these data to tumors of other sites. Salivary replacement and stringent oral hygiene should be initiated in all patients with symptomatic RT-induced xerostomia. Reagent choice should be based on patient preference and the timing of symptomatic need (i.e., day versus night).3 In addition, patients should incorporate dietary modifications including softer foods, frequent water intake, and appropriate oral hygiene practices into their daily regimen. In patients who fail to respond to these first-line treatments, pilocarpine may be initiated for those who are medically eligible. While Cevimeline may prove beneficial for post-RT patients, further studies are required. In addition to anticholinergic therapy, level I evidence suggests that acupuncture may be useful for the treatment of RT-induced xerostomia. Further studies in patients with non-nasopharyngeal primaries are required to fully delineate the utility of this therapy. Cholinergic stimulants and salivary substitutes level 1, acupuncture level 1b.